The objective of our research is to obtain new information about the etiology of insulin-dependent diabetes mellitus (IDDM) in Finland, where the incidence of IDDM is the highest in the world. During the previous 3 years we completed the collection of data on epidemiologic, HLA genetic and putative environmental risk factors from 837 consecutively registered families of a newly diagnosed child with IDDM aged 0-14 years. Statistical analyses of these data will both include descriptive epidemiology and genetics, and address for the first time the issue of interaction between genetic susceptibility and putative environmental risk factors of IDDM in a large population based study material.During the coming 3 years we will continue to analyze the collected epidemiologic and genetic data as outlined in the original grant, and will evaluate the role of environmental exposure in utero and in early life for the risk of developing IDDM by completing the two ongoing case-control studies. All non-diabetic first degree relatives in the 837 families of the newly diagnosed diabetic children will be monitored for an additional 3 years to assess the cumulative incidence of IDDM by HLA haplotype sharing. In addition, we will extend our study to analyze the risk of IDDM in the offspring of 12,325 IDDM patients. We will determine HLA genotypes in families where an IDDM parent and a child with IDDM is found in order to find out why IDDM is more often found in fathers than in mothers of diabetic children. The acetylator phenotype will also be determined in a sample of HLA genotyped families.